In recent years the quadrupole ion trap (QIT) has been becoming of great importance in analytical instrumentation. The QIT was first disclosed in 1952. The history of its development and details of its construction and operation have been set forth in various papers, including the book entitled "Quadrupole Storage Mass Spectrometry" by March and Hughes, published by John Wiley & Sons 1989. Briefly, the QIT is a mass spectrometer which employs radio frequency fields and does not require the use of a magnet for separating ions and providing a mass spectrum of an unknown sample. The sample to be analyzed is first dissociated/fragmented into ions inside the QIT, which ions are charged atoms or molecularly bound groups of atoms. The QIT is capable of providing motion restoring forces on selected ions in the three orthogonal directions and can therefore retain the selected ion inside the QIT.
There are several common techniques in use for determining the spectrum of ions in the QIT. By manipulating the electric fields within the trap, it has been possible to scan, i.e. cause consecutive values of m/e of the stored atoms to become unstable, so that the separated ions pass into a detector and the detected ion current signal intensity, as a function of the scan parameter is the mass spectrum of the ions being analyzed.
An alternative scan method employs a single supplemental dipole frequency applied to the quadrupole trapping field combined with changing the quadrupole RF field voltage so as to bring the secular motions of the trapped ions of consecutive m/e sequentially into resonance with the supplemental field causing their amplitudes to increase until the ion leave the trapping region. This method of scanning is referred to as resonance scanning. Other non-scanning spectrum determining techniques are described in another application (Varian Case No. 93-22) entitled "A Method of Space Charge Control for Improved Ion Isolation in a QIT", filed Jan. 10, 1994. These other methods include measuring image current and integrating it to determine amount of charge in the trap in a manner similar to the Ion Cyclotron Resonance Spectrometer detection (ICR) and FT-ICR or by simultaneously ejection of ions in the trap by a DC voltage applied to one end cap or setting the RF trapping voltage to zero. The simultaneously ejected ions could then be separated by the technique of ion selection employed in time-of-flight spectrometers.
There are several important experiments where it is very important to first isolate within the QIT an ion of a particular m/e or a range of such ions. One such particular experiment is called MS/MS. This is the experiment where a particular ion is isolated, as a parent ion, then the parent is dissociated by gentle collisions, generally called collision induced dissociation (CID) to obtain daughter ions. The commonly assigned U.S. Pat. No. 5,198,665 described earlier as a related patent describes one such isolation method for CID.
There are three types of sample ionization methods in common use. These are E-beam or Electron Ionization (EI), Collision Induced Dissociation (CID) and Chemical Ionization (CI). The e-beam is an adjustable energy electron beam which is caused to impact the ions at high velocity and causes violent fragmentation of a particle. CID is where the ions formed by other processes, such as EI or CI are caused to oscillate in the trap which results in collisions with a background gas resulting in the fragmentation of the ion to form an ion of smaller m/e and a neutral fragment. CI relates to a technique for inducing a chemical reaction between two different materials to form an ionic product.
To carry off a chemical ionization experiment, a neutral reagent gas is introduced into the trap and is ionized by use of an e-beam. The resulting ions of the reagent gas then react with a neutral sample to form an ion of the sample; usually by a proton transfer reaction from the reagention to the neutral sample. One problem with this approach is that the spectrum is too complex and creates several reagent ions which have different chemical properties as well as sample ions form by both EI and CI and the desired ion needs to be isolated.
It is known that species of the reagent ion have quite different properties. The different species transfer different amounts of energy to a sample molecule. Electron bombardment methods produces CH.sub.2.sup.+, CH.sub.3.sup.+, CH+.sub.4.sup.+, CH+.sub.5.sup.+, C.sub.2 H.sub.3.sup.+, C.sub.2 H.sub.4.sup.+, C.sub.2 H.sub.5.sup.+, C.sub.3 H.sub.5.sup.+. These ions are formed by direct bombardment as well as by ion molecule reactions between precursor ions of the reagent gas (formed by EI) and the remaining neutral reagent gas. Each type of ion will produce a different series of product ions when chemically ionizing a sample. Accordingly, the spectra can be very complex. There is a need to provide a single mass isolated reagent ion.
New QIT techniques for isolation of ions have been developing rapidly. However, the available techniques have drawbacks. Marshall, et al. U.S. Pat. No. 4,761,545 taught the use of an inverse Fourier transform with non-linear phasing to produce a supplemental broadband waveform which was applied to the QIT end caps. The Marshall waveform has a notch in the frequency spectrum to eject those ions from the trap whose secular resonance frequencies are outside the notch and to isolate those ions whose secular frequencies are within the notch. Franzen, et al., European patent 362432A1 teaches use of a notched broadband supplemental waveform to selectively store ions and increase their population during e-beam ionization. Kelly, U.S. Pat. No. 5,134,286 created the broadband waveform by employing uniform noise and filtering to obtain a notch. In my earlier '665 patent, a method for isolating a single narrow range of ions is disclosed employing a two step process for CID which employs the scan of the RF field in combination with a supplemental dipole field scanned resonant ejection for the lower m/e ions and a broadband waveform with no notches for ejecting the larger m/e ions. The Marshall, Franzen and Kelly approaches employ low values of RF field during ionization. This results in poor mass resolution for high mass values. My earlier method has improved high mass resolution but has a problem in that after ejection of lower m/e ions, it has no means for ejecting newly formed lower m/e ions which are created by CID during the final step of ejecting the higher mass ions. These lower m/e ions are called "shadow ions".
Louris, U.S. Pat. No. 4,686,367 discloses the method for producing CI reagent species in a trap by electron bombardment. Rejection of the ions above a selective cut-off by mass instability scanning is disclosed. Kelly, in U.S. Pat. No. 4,196,699, uses filtered noise on the end caps during ionization to eject unwanted ions of the reagent and sample gas during ionization. Weber, et al., U.S. Pat. No. 4,818,869 and Barberich, Intern. J. Mass. Spec. and Ion Proc. V 94, P. 115-147 (1989) teaches ion isolation by a method to mass select the CI reagent ion after the end of the initial ion formation period, i.e. the ionization time plus a precursor reaction period. In this method, the precursor ions, which themselves may be reagent ions must be in the trap to form other species of reagent ions. After the end of the reagent formation period, a DC pulse is applied. This does not prevent the formation of additional low mass reagent ions by charge exchange or ion forming processor after the DC pulse mass isolation step. Also, the filtered noise method of the Kelley patent must allow the trapping of all the precursor ions since it is on only during the e-beam ionization step, period A of FIG. 4 of '689 patent, and is off during the reaction step, period B in FIG. 4 of '689 patent. Accordingly, Kelly also has no provision for isolation of a single mass isolated reagent species, without also isolating all precursor ions that lead to the formation of the desired reagent ions.